AGING EFFECT ON PREADIPOCYTE DIFFERENTIATION

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from the Applicant's Abstract): It is hypothesized
that C/EBPalpha, a key transcription factor that controls both initiation of
adipogenesis and maintenance of the fat cell phenotype, plays a central role
in the age-related decrease in preadipocyte differentiation and lipid
accumulation.

Specific Aim 1 of the investigators is to determine effects of aging on
expression and activity of C/EBPalpha and transcription factors regulating
its expression during preadipocyte differentiation. They will define
changes in the mRNA and protein levels and functional properties of
C/EBPalpha and potential C/EBPalpha regulators (CHOP, C/EBPbeta-LIP and LAP,
C/EBPbeta, CUP, c-myc, PPARy:RXRa) using Northern blot, Western blot and in
vitro DNA binding assays respectively in differentiating preadipocytes from
3 and 24m rats. These experiments will 1) establish temporal relationships
among age-related changes in expression of C/EBPalpha, C/EBPalpha
regulators, selected differentiation-dependent target genes, and lipid
accumulation (TG/DNA ratio) and 2) identify those C/EBPalpha regulators
which change in amount or activity during aging.

Specific Aim 2 is to determine whether age-related changes in preadipocyte
differentiation are caused directly by alterations in C/EBPalpha and
C/EBPalpha regulator levels and/or activity. Two experimental approaches
will be used: 1) treatment of preadipocytes with agents known to alter
C/EBPalpha expression (TNFa converting enzyme inhibitors, glucocorticoids,
SB203580, thiazolidinediones) and 2) transfection of appropriate DNA
constructs to alter levels of C/EBPalpha and those C/EBPalpha regulators
identified in Specific Aim 1 that influence related changes in expression.

Specific Aim 3 is to assess the relevance of their findings to humans. They
will determine in human preadipocytes whether changes in
differentiation-dependent mRNA levels are blunted with age and if C/EBPalpha
expression and activity decline with age.
StatusFinished
Effective start/end date5/15/973/31/21

Funding

  • National Institute on Aging
  • National Institute on Aging
  • National Institute on Aging: $309,755.00
  • National Institute on Aging: $322,000.00
  • National Institute on Aging
  • National Institute on Aging: $322,000.00
  • National Institute on Aging: $322,000.00
  • National Institute on Aging: $98,188.00
  • National Institute on Aging: $321,417.00
  • National Institute on Aging: $417,790.00
  • National Institute on Aging: $272,155.00

ASJC

  • Medicine(all)

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